Use of CD83 in Combination Therapies

Abstract

The present invention relates to improved methods of suppressing and/or preventing an undesired immune response comprising the use of CD83. In some embodiments, CD83 is coadministered to a subject with at least one other immunosuppressive compound. Methods are also provided for generating tolerogenic dendritic cells and regulatory T cells. These cells can be used in vitro to produce additional cells for therapeutic purposes or they can be used in vivo to suppress and/or prevent an undesired immune response. Methods of the invention can be used to prevent or reduce the severity of autoimmune diseases and can also be used to induce tolerance to at least one therapeutic composition, such as a therapeutic protein or transplanted tissue.

1 . (canceled) 
     
     
         2 . A method of treating a subject to prevent, cure, or alleviate at least one symptom of a disease or disorder caused by the dysfunction or undesired function of an immune response in a subject comprising the step of co-administering soluble CD83 and a first immunosuppressive compound to the subject, wherein said first immunosuppressive compound is selected from the group consisting of cyclosporine, tacrolimus, sirolimus, and anti-CD45RB mAb. 
     
     
         3 . The method of  claim 2 , wherein said soluble CD83 and said first immunosuppressive compound are administered in different formulations and via different routes of administration. 
     
     
         4 . The method of  claim 2 , wherein said first immunosuppressive compound is cyclosporine. 
     
     
         5 . The method of  claim 2 , wherein said soluble CD83 and said first immunosuppressive compound are co-administered with a second immunosuppressive compound, wherein:
 (a) said first immunosuppressive compound is sirolimus and said second immunosuppressive compound is anti-CD45RB mAb; or   (b) said first immunosuppressive compound is tacrolimus and said second immunosuppressive compound is mycophenolate mofetil.   
     
     
         6 . The method of  claim 3 , wherein said soluble CD83 and said first immunosuppressive compound are administered within three days of each other. 
     
     
         7 . The method of  claim 2 , wherein said disease or disorder is an autoimmune disease. 
     
     
         8 . The method of  claim 5 , wherein said soluble CD83 is administered separately to the subject from said first immunosuppressive compound and said second immunosuppressive compound. 
     
     
         9 . The method of  claim 2 , wherein said disease or disorder is rejection of tissue from a transplant recipient, and wherein the soluble CD83 is administered to the transplant recipient: (a) with the tissue; or (b) following the transplantation of the tissue; or (c) both with the tissue and following the transplantation of the tissue. 
     
     
         10 . The method of  claim 9 , further comprising the coadministration of said soluble CD83 to said recipient with an antigen associated with the transplanted tissue. 
     
     
         11 . A method of decreasing the amount of an immunosuppressive compound used to treat a subject during at least one treatment interval comprising the step of co-administering soluble CD83 to said subject with said immunosuppressive compound. 
     
     
         12 . The method of  claim 11 , wherein said immunosuppressive compound is cyclosporine. 
     
     
         13 . The method of  claim 11 , wherein said immunosuppressive compound is sirolimus and wherein said method further comprises the step of coadministering anti-CD45 RB mAb to said subject. 
     
     
         14 . The method of  claim 11 , wherein said immunosuppressive compound is tacrolimus and wherein said method further comprises the step of coadministering mycophenolate mofetil to said subject. 
     
     
         15 . A method of preventing rejection in a transplant recipient of transplanted tissue comprising the step of exposing a tissue after removal from a transplant donor to a solution comprising sCD83. 
     
     
         16 . The method of  claim 15 , wherein said method further comprises the step of co-administering a solution comprising sCD83 to the transplant recipient with the transplanted tissue, wherein said solution is co-administered in combination with another immunosuppressive compound selected from the group consisting of cyclosporine, tacrolimus, sirolimus, and anti-CD45RB mAb. 
     
     
         17 . The method of  claim 16  wherein said solution is co-administered to the transplant recipient in combination with:
 (a) tacrolimus and mycophenolate mofetil; or 
 (b) sirolimus and anti-CD45RB mAb.